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Genetic Determinants of Orofacial Shape and Relationship to Cleft Lip/Palate

Key Personnel

Richard Spritz
University of Colorado - Denver
Richard.Spritz AT

Benedikt Hallgrimsson
University of Calgary

Ophir Klein (PI/MPI)
University of California, San Francisco
Ophir.Klein AT

Project Features

Data Types:
Facial Images/Landmarks, microCT Images
Grant #:
U01 DE020054

Featured Contributions

Featured Presentations

Data Description

This project provides genetic information, images and morphometric data for both mus musculus and homo sapiens to the FaceBase Hub. The initial data provided consists of images of the skulls of adult mice from the Collaborative Cross (CC), a large panel of recombinant inbred strains derived from a genetically diverse set of founder strains and designed specifically for complex trait analysis ( Each data set includes images of mice from the same genetic background. Adult crania are scanned in the Scanco Medical μCT 35 at 35 μm.

The background strains used in the collaborative cross are listed below, with links to Jackson Lab descriptions:

For each mouse, the dataset includes four files: • An AIM-format file. The AIM format is similar to .RAW and can be viewed with software from Amira • A .hx file • A .txt file containing detailed image processing data. The dataset also includes a movie file (.avi) that provides a 3-dimensional view of the skull of a representative animal from this cross, and a metadata file that describes all of the collaborative cross mice submitted from this FaceBase project to date.


Orofacial clefts, principally cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP), are among the most common major birth defects, occurring in ~1/700 to 1/1000 live births in various populations around the world, ~70% as a sporadic, isolated abnormality. Such "non-syndromic" orofacial clefts act as complex traits, involving multiple genes and environmental risk factors. To date traditional genetic mapping approaches have identified only a few major susceptibility genes for non-syndromic orofacial clefts with certainty. Therefore, new approaches are clearly required.

There is considerable evidence that orofacial malformations can occur at the extremes of the normal ranges of phenotypic variation of midfacial size and shape. Here we propose a novel approach to identify genes that regulate midfacial shape in mouse and human. We hypothesize that genes that are major contributors to normal orofacial size and shape will also have important roles in the occurrence of orofacial clefts.

To identify such genes, we will perform detailed morphometric analysis of midfacial shape differences in informative mouse strains as well as in select human populations, combining these studies with genetic analyses to identify genes that control major determinants of midfacial morphometries. Our studies have shown that specific inbred strains of mice have heritable differences in measurable parameters of facial shape. We will take advantage of a valuable new resource we have developed, the mouse "Collaborative Cross" (CC), to con-elate heritable differences in facial shape among the 8 founder strains of the CC, along with select Recombinant Inbred lines and Recombinant Intercross (RIX), with detailed genetic mapping data for these mice. This approach will enable identification of quantitative trait loci (QTLs) that underlie these morphometric differences.

We will complement our mouse studies with a similar analysis of humans, studying specific populations with different susceptibilities to orofacial clefts. These comparative studies will allow us to identify genes that underlie midfacial shape in humans. Together, these studies should provide a basis for understanding the relationship between human facial morphogenesis and susceptibility to orofacial clefts, and for initiating studies of the functions of these genes in animal models relevant to human orofacial development.

Data is now available. Please contact help AT with your request to receive further information.